The objective of this work is to understand the biochemical and biophysical bases of neutrophil adhesion under hydrodynamic flow which make neutrophils ideal as mediators of the acute inflammatory response. Because neutrophils are blood cells which bind to the vascular wall to perform their inflammatory role, this work clearly fits directly in the central theme of the Program Project to investigate interactions of blood cells with vascular components, such as endothelial cells which line blood vessels and other leukocytes suspended in blood. However, it also extends and supplements the approaches offered by other investigators in the Program Project to a new, very important blood cell type involved in the immunological defense of disease (Harlan, 1985; Anderson and Springer, 1984) and responsible for auto-immune disorders (Edington, 1992). Three areas of science essential to this endeavor are 1) biochemistry, to determine the biochemical properties of molecules involved in neutrophil adhesion; 2) mechanics, to determine the mechanical properties of neutrophils and their membranes, and to study the micromechanical response of adhesion molecules to force and strain; and 3) fluid mechanics, to determine the hydrodynamic forces acting on blood cells in the microcirculation. Each of these areas is a focus of collaboration between Dr. Hammer and other investigators in the Program Project. For example, investigations of the mechanical properties of individual adhesion molecules will be performed in collaboration with Dr. R. E. Waugh, who invented one of the techniques to be used for these measurements. Also, measurement of adhesion properties of neutrophils requires detailed measurements of neutrophil deformation in which neutrophil volume is carefully regulated, performed in conjunction with Dr. Waugh and Dr. P. Knauf. Finally, measurement of the hydrodynamic forces seen by individual cells in the microcirculation is aided by interactions with Dr. Sarelius.